Human skin, in particular the outer layer, the stratum corneum, provides an effective barrier against penetration of microbial pathogens and toxic chemicals. While this property of skin is generally beneficial, it complicates the dermal administration of pharmaceuticals in that a large quantity, if not most, of an active ingredient applied on the skin of a patient suffering from a dermal disease may not penetrate into the viable layers of the skin where it exerts its activity. To ensure an adequate penetration of the active ingredient into the dermis and epidermis, it is generally preferred to include the active ingredient in a dissolved state, typically in the presence of a low-molecular volatile solvent such as an alcohol, e.g. ethanol, or a diol, e.g. propylene glycol, which may also act as a penetration enhancer for the active ingredient. Another way to obtain penetration of the active ingredient into the skin is to provide occlusion by formulating the active ingredient in a hydrophobic vehicle such as petrolatum. However, ointments containing petrolatum generally have a tacky or greasy feel that persists for quite some time after application, and are consequently not cosmetically acceptable.
As an alternative to conventional formulations such as ointments, compositions containing film-forming polymers in which an active ingredient has been incorporated have been developed. Film-forming compositions have mainly been used to provide transdermal delivery of an active ingredient such as in transdermal patches or, more recently, as film-forming solutions composed of a film-forming polymer, a plasticiser and a low-molecular volatile solvent for the active ingredient. When the solution is applied on skin, a thin polymeric film is formed after evaporation of the solvent.
EP 515 312 B1 discloses a topical formulation containing terbinafine as the active ingredient and a film-forming polymer, e.g. polyvinylacetate or acrylic and methacrylic acid ester copolymers, for use as a nail varnish in the treatment of onchomycosis.
WO 2006/111426 discloses a film-forming solution containing a vitamin D derivative and a corticosteroid for use as a nail varnish in the treatment of nail psoriasis. The film-forming polymer may be selected from polyvinylpyrrolidone, butyl ester of polyvinyl methyl ether and maleic acid copolymer and acrylate and ammonium methacrylate copolymer. The composition may contain ethanol as a solvent and may additionally contain a penetration enhancer.
US 2007/0248658 discloses compositions comprising film-forming polyurethanes or polyurethane and acrylate copolymers and one or more active ingredients for use in dermal or transdermal delivery of the active ingredient(s) such as ethinylestradiol. The composition may additionally contain a low-molecular volatile solvent such as ethanol or isopropanol and a penetration enhancer such as oleic acid, oleyl alcohol, propylene glycol propylene carbonate, N-methylpyrrolidone and isopropyl myristate.
US 2004/0213744 discloses a sprayable composition for topical application comprising a film-forming polymer, a permeation enhancer, a solubilizer, a plasticizer and an active ingredient. The film-forming polymer may be an acrylic polymer or copolymer, a methacrylic acid polymer or copolymer, polyvinylacetate, polyvinyl alcohol, polyvinylpyrrolidone or a cellulose polymer. The permeation enhancer may be selected from surfactants, oleic acid, mixed esters of capric and caprylic acid, polyhydric alcohols, isopropyl myristate etc. The solubilizer may be a surfactant, polyhydric alcohol or a copolymer of dimethylamine ethyl methacrylate and methacrylic acid ester copolymer. The plasticizer may be selected from triethyl citrate, dimethyl isosorbide, acetyl tributyl citrate, castor oil, propylene glycol etc. The composition may further include a propellant, e.g. hydrocarbon, hydrofluorocarbon, dimethylether, nitrogen, carbon dioxide, etc.
WO 2007/031753 discloses a film-forming composition comprising an active ingredient which is present in at least 80% saturation, a film-forming polymer such as polyvinylpyrrolidone, polyvinyl alcohol, acrylic polymers and copolymers, methacrylic polymers and copolymers and cellulose polymers, a low-molecular volatile solvent such as ethanol, a propellant such as hydrofluoroalkane, and preferably also an antinucleating agent such as polyvinyl alcohol and a plasticizer such as glycerol, polyethylene glycol, oleic acid, citric acid, fatty acid esters, hydrocarbons etc.
An object of the present invention is to provide film-forming compositions that are thin and transparent so that they form a nearly invisible film on the skin, the film being flexible, fast drying and non-sticky.
Another object of the invention is to provide film-forming compositions that are capable of releasing an active ingredient incorporated therein over a prolonged period of time into the upper layers of the skin so that the composition may be administered less frequently than conventional topical compositions such as creams, ointments or gels.
Another object of the invention is to provide a film-forming composition with improved penetration of the active ingredient incorporated therein into the upper layers of the skin, especially the stratum corneum, in the absence of conventional penetration enhancers such as alcohols or propylene glycol which are potential skin irritants. The stratum corneum may in this case function as a reservoir from which the active ingredient is gradually released.
A further object of the invention is to provide a composition in which the active ingredient will not be significantly degraded, but remains chemically and physically stable throughout the shelf-life of the composition.